Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Improved Survival of Children, Adolescents, and Young Adults With Head and Neck Soft Tissue Sarcomas in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Eva Clemens
  • Linda Broer
  • Thorsten Langer
  • André G Uitterlinden
  • Andrica C H de Vries
  • Martine van Grotel
  • Saskia F M Pluijm
  • Harald Binder
  • Julianne Byrne
  • Eline van Dulmen-den Broeder
  • Marco Crocco
  • Desiree Grabow
  • Peter Kaatsch
  • Melanie Kaiser
  • Line Kenborg
  • Jeanette F Winther
  • Catherine Rechnitzer
  • Henrik Hasle
  • Tomas Kepak
  • Anne-Lotte F van der Kooi
  • Leontien C Kremer
  • Jarmila Kruseova
  • Claudia E Kuehni
  • Heleen van der Pal
  • Ross Parfitt
  • Dirk Deuster
  • Peter Matulat
  • Claudia Spix
  • Amelie Tillmanns
  • Wim J E Tissing
  • Lara Maier
  • Antoinette Am Zehnhoff-Dinnesen
  • Oliver Zolk
  • Marry M van den Heuvel-Eibrink
  • PanCareLIFE consortium
Vis graf over relationer

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8-21.5; P = 5.6 × 10-7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3-4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04-14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07-2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

OriginalsprogEngelsk
TidsskriftThe pharmacogenomics journal
Vol/bind20
Udgave nummer2
Sider (fra-til)294-305
Antal sider12
ISSN1470-269X
DOI
StatusUdgivet - apr. 2020

ID: 59231758